There is a form of sporadic obesity that is a member of the "contiguous gene syndrome" the Prader-Willi syndrome (PWS). PWS itself is a sporadic disorder that is associated with a cytogenetic microdeletion on chromosome 15 at band q11.2. Half the patients have recognizable cytologic deletion and since there is molecular evidence for heterogeneity in breakpoint It is presumed that the cytogenetically normal patients have sub-microscopic deletions. The clinical heterogeneity reported in PWS suggests that differences in deletion breakpoints lead to variation in phenotype. There have also been reports of cytogenetic deletions of 15q11.2 in patients who have non-familial (sporadic) truncal obesity with out PWS. Molecular studies using DNA probes from 15q11.2 have detected deletions in other patients with sporadic truncal obesity; these deletions appear to be much smaller than those encountered in PWS. This information supports the belief that there is a gene for sporadic obesity, one of several features found in the Prader-Willi syndrome, localized within or near 15q11.2. Recent advances in methodologies for the targeted amplification of specific regions of the genome will allow the direct isolation of DNA segments from chromosome 15 without the need for library screening. Amplified of DNA sequences from pulse-field gel electrophoresis fragments will be used to construct phenotype/deletion maps of patients samples using quantitative in situ hybridization. This will serve to resolutely map a "critical region" for obesity and to orient it with respect to the full PWS "critical region" so that these putative obesity gene(s) may be isolated. The methods that will be used in this project take into account the previous difficulties encountered in the cloning of segments from this unstable region of the genome and will permit the elucidation of deletion maps for abnormal phenotypes. It is postulated that high-risk genotypes will be defined in some families of sporadic obesity and that these genotypes may be used to assess individual risks for this particular type of obesity. In addition, these genetic markers will help to elucidate the mechanisms for genetic deletions and how they relate to other syndromes localized to chromosome 15q11.2.